scholarly journals Ruolo del citrato nel metabolismo osseo

2020 ◽  
Vol 32 (1) ◽  
pp. 15-20
Author(s):  
Giuseppe Vezzoli ◽  
Giulia Magni ◽  
Monica Avino ◽  
Teresa Arcidiacono
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Calcium Ions ◽  
Soft Tissues ◽  
Tricarboxylic Acid Cycle ◽  
Organic Matrix ◽  
Volumetric Bone Mineral Density ◽  
Acid Base Balance ◽  
Mineral Density

Citrate is an organic compound involved in tricarboxylic acid cycle, regulation of acid-base balance, lipid metabolism and bone formation. The 90% of body citrate is deposited in bone tissue and is released with calcium ions during bone resorption; therefore, bone resorption contributes to maintain normal plasma levels of citrate together with kidney excretion. The parallel release of citrate and calcium from bones decreases the possibility of calcium-phosphate precipitation in soft tissues, as citrate can bind calcium ions in organic fluids. Citrate may also take part to the bone formation as it sustains the correct mineralization of bone organic matrix: its molecule binds calcium ions at the surface of hydroxyapatite nanocrystals and maintains the correct spatial disposition of nanocrystals, thus, stabilizing the structure of bone lamellae and sustaining biomechanical characteristics of bone tissue. Multiple studies observed that citrate administration significantly increased areal and volumetric bone mineral density at different locations of 1-2% per year and improved bone resorption markers as well. Therefore, it has been hypothesised a therapeutic role of citrate in osteoporosis; however, this role has to be better clarified to understand its real anti-fracture effect.

scholarly journals ASSESSMENT OF THE STATUS OF BONE TISSUE IN THE WORKING VIBRATION THREATENING OCCUPATIONS

2018 ◽  
Vol 97 (6) ◽  
pp. 542-546 ◽  
Author(s):  
Anna V. Sukhova ◽  
E. N. Kryuchkova
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Biochemical Markers ◽  
Clinical Laboratory ◽  
Mineral Metabolism ◽  
Epidemiological Studies ◽  
Mineral Density ◽  
Local Vibration ◽  
Vibration Disease

Introduction. Vibration in conjunction with an unfavorable microclimate and physical stress, acting on mining workers, can lead to the development of pathology of the musculoskeletal system with the violation of bone metabolism and the formation of the osteopenic syndrome. The results of epidemiological studies indicate a high prevalence of osteoporosis among persons of working age. The purpose of the study was to study the effect of the general and local vibration on the state of bone remodeling processes in workers of vibration-hazardous occupations. Material and methods. Two groups of patients with vibration disease were examined. The first group consisted of 53 cases working in the contact with local vibration. The second group included 52 workers exposed to combined effects of the general and local vibration. The condition of the osteoarticular apparatus was determined by means of by X-ray examination and ultrasonic osteodensitometry. Laboratory studies included the evaluation of indices of mineral metabolism and bone tissue metabolism. Results. Osteochondrosis of the spine was revealed in 54.7% and 69.2%, osteopenia of the spine - 17.0% and 21.2%, arthrosis of the joints of the hands - 64.2% and 57.7% in the patients of the first and second groups, respectively. The prevalence rate of bone-dystrophic changes depends on the stage of the vibration disease and increases as the disease progresses. There were established interrelations of clinical functional and clinical laboratory indices with the trainee exposure of industrial vibration in terms of bone mineral density (T and Z criteria) (r = 0.56), biochemical markers of bone formation (r = -0.62-0.70) and bone resorption (r = 0.72-0.85). Biochemical markers of the osteopenic syndrome in the vibration disease are bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine). Discussion. The obtained results served as a basis for developing a system of preventive measures of bone-dystrophic disorders in persons with vibration dangerous occupations.

Changes in bone metabolism associated with exposure to industrial vibration

2020 ◽  
pp. 766-766
Author(s):  
A. V. Sukhova ◽  
E. N. Kryuchkova
Keyword(s):  
Bone Mineral Density ◽  
Alkaline Phosphatase ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Metabolism ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Local Vibration ◽  
Markers Of Bone Formation

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.

Biological Response to Wollastonite Doped α-Tricalcium Phosphate Implants in Hard and Soft Tissues in Rats

2008 ◽  
Vol 396-398 ◽  
pp. 7-10 ◽  
Author(s):  
Ana Maria Minarelli Gaspar ◽  
Sybele Saska ◽  
R. García Carrodeguas ◽  
A.H. De Aza ◽  
P. Pena ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Bone Formation ◽  
Bone Tissue ◽  
Tricalcium Phosphate ◽  
Rattus Norvegicus ◽  
Soft Tissues ◽  
Subcutaneous Tissue ◽  
Biological Response ◽  
New Bone Formation ◽  
Rat Bone

The biological response following subcutaneous and bone implantation of β-wollastonite(β-W)-doped α-tricalcium phosphate bioceramics in rats was evaluated. Tested materials were: tricalcium phosphate (TCP), consisting of a mixture of α- and β-polymorphs; TCP doped with 5 wt. % of β-W (TCP5W), composed of α-TCP as only crystalline phase; and TCP doped with 15 wt. % of β-W (TCP15), containing crystalline α-TCP and β-W. Cylinders of 2x1 mm were implanted in tibiae and backs of adult male Rattus norvegicus, Holtzman rats. After 7, 30 and 120 days, animals were sacrificed and the tissue blocks containing the implants were excised, fixed and processed for histological examination. TCP, TCP5W and TCP15W implants were biocompatible but neither bioactive nor biodegradable in rat subcutaneous tissue. They were not osteoinductive in connective tissue either. However, in rat bone tissue β-W-doped α-TCP implants (TCP5W and TCP15W) were bioactive, biodegradable and osteoconductive. The rates of biodegradation and new bone formation observed for TCP5W and TCP15W implants in rat bone tissue were greater than for non-doped TCP.

scholarly journals Osteoporosis and diabetes mellitus

2013 ◽  
pp. 63-69
Author(s):  
Andrea Montagnani ◽  
Massimo Alessandri
Keyword(s):  
Diabetes Mellitus ◽  
Bone Resorption ◽  
Bone Tissue ◽  
Close Association ◽  
Normal Population ◽  
Diabetic Patients ◽  
Mineral Density ◽  
Apparent Paradox ◽  
Mortality And Morbidity ◽  
Positive Effects

Introduction: Diabetes mellitus (DM) and osteoporotic fractures are major causes of mortality and morbidity in older subjects. Recent reports have revealed close association between fracture risk and DM types 1 and 2 (DM1 and DM2, respectively). Aim of this review is to highlight the importance of these diseases in the elderly and examine certain etiopathogenetic aspects of DM associated osteoporosis, which could be useful in management of diabetic patients. Materials and methods: We searched the Embase and PubMed databases using diabetes, osteoporosis, and bone mineral density (BMD) as search terms and 1989-2009 as publication dates. Discussion: The risk of fractures seems to be increased in both types of DM although DM2 seems to be associated with normal-high BMDs compared with the normal population. This apparent paradox could reflect greater bone frailty in diabetic patients that are unrelated to adipose tissue, hyperinsulinemia, deposition of advanced glycosylation end products in collagen, reduced serum IGF-1 levels, hypercalciuria, renal failure, microangiopathy, and/or inflammation. Diabetic patients’ propensity to fall and multiple comorbidities might also explain their higher fracture rates. The effects of drugs that inhibit bone resorption in diabetic patients are probably similar to those obtained in nondiabetics although there is little information on this issue. In general, effective treatment of diabetes has positive effects on bone metabolism. Metformin acts directly on bone tissue, reducing AGE accumulation, and insulin has direct effects on osteoclast activity. In contrast, the thiazolidinediones seem to have negative effects since they orient mesenchymal progenitor cell differentiation toward adipose rather than bone tissue. Incretin therapy is a newer approach that appears to modify interactions between nutrition and bone turnover (e.g., postprandial suppression of bone resorption). Conclusions: Better understanding of how diabetes and its treatment influence bone tissue could lead to more effective strategies for preventing fractures in diabetic patients. More investigation is needed to determine whether conventional osteoporotic therapy is fully effective in patients with DM.

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis

2020 ◽  
Vol 77 (23) ◽  
pp. 1949-1956
Author(s):  
Caitlin Prather ◽  
Erin Adams ◽  
Whitney Zentgraf
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Bone Resorption ◽  
Bone Formation ◽  
English Language ◽  
Safety Concern ◽  
Osteoporotic Fractures ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Poster Presentations

Abstract Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the sclerostin inhibitor romosozumab for the treatment of osteoporosis, including data from clinical trials of the drug. Summary A review of the literature was performed by searching PubMed and MEDLINE for all relevant articles published between January 2014 and February 2020 using the keywords romosozumab, romosozumab-aqqg, osteoporosis, and fracture. All relevant English-language articles evaluating the pharmacology, efficacy, or safety of romosozumab for the treatment of osteoporosis in humans were included; poster presentations were excluded. Romosozumab has been approved by the Food and Drug Administration and is considered both safe and effective for the treatment of osteoporosis in high-risk postmenopausal females. Phase 2 and phase 3 clinical trials have shown a statistically significant decrease in new vertebral fractures and an increase in bone mineral density with romosozumab use, as compared with both placebo use and use of alternative osteoporosis therapies. The primary safety concern is a potential risk of cardiovascular events; additionally, hypocalcemia must be corrected prior to initiation. Romosozumab is the first anabolic medication that both increases bone formation and decreases bone resorption. Data suggest that romosozumab is more effective than oral bisphosphonates in preventing osteoporotic fractures, though cost and safety concerns must be considered. Conclusion Romosozumab is a novel, 12-month treatment option for postmenopausal women at high risk for osteoporotic fracture that both increases bone formation and decreases bone resorption.

scholarly journals Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial

2013 ◽  
Vol 98 (2) ◽  
pp. 571-580 ◽  
Author(s):  
Kim Brixen ◽  
Roland Chapurlat ◽  
Angela M. Cheung ◽  
Tony M. Keaveny ◽  
Thomas Fuerst ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Resorption ◽  
Bone Formation ◽  
Postmenopausal Women ◽  
Bone Strength ◽  
Bone Mineral ◽  
Bone Resorption Marker ◽  
Mineral Density ◽  
Volumetric Bmd ◽  
The Impact

Abstract Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys. Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine. Design: This was a randomized, double-blind, 2-year trial. Setting: The study was conducted at a private or institutional practice. Participants: Participants included 214 postmenopausal women with low areal BMD. Intervention: The intervention included odanacatib 50 mg or placebo weekly. Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured. Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P &lt; .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P &lt; .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P &lt; .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P &lt; .001 at 24 months). Adverse experiences were similar between groups. Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

An increase in bone stability in an aripiprazole add-on or switching study

2011 ◽  
Vol 26 (S2) ◽  
pp. 1257-1257 ◽  
Author(s):  
S. Masand ◽  
R. Sherwood ◽  
K.J. Aitchison
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Partial Agonist ◽  
Bone Alkaline Phosphatase ◽  
Mental Health Disorder ◽  
Mineral Density ◽  
Open Label ◽  
Urinary Markers ◽  
Osteoblastic Activity

IntroductionSchizophrenia is a mental health disorder associated with high rates of osteoporosis. Studies have suggested antipsychotics as a major cause of accelerated decrease in bone mineral density.Oestrogen deficiency contributes to osteoporosis and causes increased osteoclast numbers/osteoclastic activity. Prolactin suppresses hypothalamo-pituitary-ovarian axis activity, leading to decreased oestrogen concentrations.Aripiprazole, an ‘atypical’ antipsychotic, is a partial agonist at dopamine D2-receptors, while other atypical antipsychotics are antagonists at these receptors. Dopamine inhibits prolactin release via these receptors at the anterior pituitary. Aripiprazole has been found to decrease prolactin concentrations in chronic schizophrenics and may be protective against osteoporosis.Quantitation of specific markers of osteoclastic (cross-linked N-telopeptide (NTX)) and osteoblastic activity (bone alkaline phosphatase (BAP)) can be correlated with bone resorption and bone formation, respectively.ObjectivesExploring whether aripiprazole is effective in stabilising bone turnover.AimsInvestigate changes in urinary markers of bone turnover.MethodsWe performed 52 week, open-label, intention-to-treat study, offering either a switch to aripiprazole or aripiprazole as add-on to initial antipsychotic medication.Serial measurements of prolactin, testosterone, 17-β-oestradiol, serum BAP, albumin, urinary creatinine, and urinary NTX concentrations were taken between 0 and 52 weeks.ResultsAt the end-point of study, versus the baseline, there were significant decreases in concentrations of urinary markers of bone resorption (P = 0.002 for NTX) and bone formation (P = .026 for BAP). Additionally, a significant decrease in prolactin (P = 0.004) and significant increase in 17-β-oestradiol concentrations (P = 0.015) were found.ConclusionsOur results show decreased overall bone turnover; and increased long-term bone stability in patients who changed medication.

scholarly journals Comparable Effects of Strontium Ranelate and Alendronate Treatment on Fracture Reduction in a Mouse Model of Osteogenesis Imperfecta

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Changgui Shi ◽  
Bin Sun ◽  
Chao Ma ◽  
Huiqiao Wu ◽  
Rui Chen ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Mouse Model ◽  
Bone Formation ◽  
Osteogenesis Imperfecta ◽  
Strontium Ranelate ◽  
Maximum Load ◽  
Inhibitory Effect ◽  
Comparable Efficacy ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density

Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.

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